Team:TU Eindhoven/Project

This year’s iGEM team of the Eindhoven University of Technology focuses on a fundamental problem in the application of genetically modified bacteria inside the human body – the immune system. Locally bacterial produced drugs are a promising future in the field of medical treatments. However, this local drug release and production requires bacterial life forms inside the human body and these bacteria can cause immune responses. This natural immune system can be evaded with the use of two methods: suppression of the entire immune system or modifying the used bacteria in order to minimise the immune systems’ response. Due to the devastating impact of the first possibility, iGEM 2014 team Eindhoven decided to proceed with the second option.

Bacteria can be made undetectable to the immune system with the use of encapsulation. Hydrogels are suitable for this purpose. Hydrogels are water-absorbing (synthetic) polymers, and are therefore able to form a layer around the bacteria. Due the low reactivity of this hydrogel capsule towards the immune system and permeability to small essential molecules (for example nutrients and wastes). With the use of microfluidic techniques, the amount of bacterial cells per liquid droplet is relatively easy to control. In the produced microfluidic droplet, hydrogel formation can be induced. The result is a hydrogelation from the outside towards the core of the droplet, surrounding the entire group of bacteria. The problems with these current techniques are: inhomogeneous hydrogelation (due to gelation form the outside to the core), uncontrollable cell growth inside the encapsulation, thus incontrollable drug release, and non-degradable encapsulations. The conventional encapsulation technique is visualised in Figure 1.

Figure 1

Our goal is to genetically engineer an E. coli bacteria strain in which each bacterium is able to produce a hydrogel capsule around its entire cell membrane, with the help of microfluidic techniques, in order to evade the immune system. This is visualised in Figure 2. A criterion that must be met is the fact that this engineered E. coli must produce a degradable capsule, either enzymatically or after a certain induction. The advantages of this technique are a possible gelation from the inside toward the outside (a more homogeneous gelation process), a controllable cell growth (only one bacterium per capsule), and the bacterium will be able to control its own polymerisation process enzymatically – this will result in more controllable drug release.

Figure 2